Bile acids (BA) are increasingly being appreciated beyond their lipid solubilizing properties as complex signaling molecules that are intricately involved in the regulation of metabolic homeostasis. Accumulation of BAs is also known to be a driving force behind cholestatic liver injuries. Although mouse models have long been used to study important aspects of BA metabolism, there are substantial differences between humans and mice in terms of BA pool composition and signaling potential, highlighting the difficulties in directly extrapolating mice findings to BArelated liver diseases in humans.
For example, compared with humans, rodents possess a significantly more hydrophilic BA pool because of the abundant presence of muricholic acids, a set of primary BAs hydroxylated at the 6-β position, making them much more water-soluble and less injurious. This, along with other species differences in BA composition, may explain why murine models of cholestasis fail to recapitulate the totality or severity of human diseases, and points to the urgent need to develop mouse models with “humanized” BA pool.
Read the Xiao Zhao editorial: https://www.cmghjournal.org/article/S2352-345X(21)00011-4/fulltext
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